Regulation of bone growth with application of zeolite in combination with bone transplant substitutes
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to chemical-pharmaceutical industry and represents substitute of bone transplant, containing osteogenic agent and zeolite, which contains particles, containing ion-exchange cations of metals, present in quantity, effective for stimulation of osteogenesis in patient who needs it, in which said metal cations are selected from the group, consisting of zinc ions, silver ions, copper ions and their combinations.
EFFECT: invention provides optimal delivery of cations into injured region with resulting formation of healthy bone tissue.
This application claims priority in accordance with the provisional application for U.S. patent No. 61/211569 filed April 1, 2009, and provisional application for U.S. patent No. 61/309143 filed March 1, 2010, the full disclosure of which is incorporated into this description by reference.
The LEVEL of TECHNOLOGY
The achievement of successful bone formation between different structures (for example, fragments of the fracture of the implants in the bone) is the main goal of many orthopedic, maxillofacial and spinal procedures. In the result it was assumed that the different methods, proteins and implants that stimulate osteogenesis, can play a significant role in achieving favorable outcomes after these operations.
Bone grafts are used to provide structured support to fill the voids and to improve the biological reconstruction of defects of the skeleton. Bone autograft is taken from one person and transplanted to another location in the body to stimulate bone formation. The advantage of autograft is that he is a native tissue of the patient, and this material is associated with the highest probability of successful healing. However, this intervention may give rise to many complications, such as infection, bleeding, chronic pain in the donor area, R is sriv and damage to the neurovascular structures. Another disadvantage of autologous bone graft in that it is available only in limited quantities. The allograft is bone, which was taken from a corpse that eliminates most of the morbidity associated with bone autograft. However, this tissue is missing in osteogenic properties of autograft and there are inherent risks or transmission of infectious diseases or immunological reactions. Although these grafts have been shown to stimulate bone formation, both of these strategies demonstrate various disadvantages.
For these reasons, developed other materials that either help or even replace autograft. Demineralized bone matrix (DBMs) is obtained by acid extraction of the cortical layer of the bone; there is an assumption that the removal of the mineral phase (i.e. calcium and phosphate) can release present in the matrix osteoinductive proteins, including bone morphogenetic proteins (BMPs). Demineralized bone matrix (DBMs), typically used with bone autograft as a filler for bone graft. Another class of fillers bone graft is ceramics and other synthetic materials.
By definition, an ideal bone graft should the region is to give as excellent osteoconductive, and osteoinductive properties after the introduction of the operative field. Osteoconductive framework supports the inflow of osteogenic cells and the formation of new blood vessels, which creates an environment that promotes bone growth. Osteoinductive proteins can facilitate the formation of new bone, stimulating the differentiation of stem cells into osteoblasts. In order to be considered osteoinductive, the substance must contain one or more biologically active signaling molecules so that the concentration of these factors could ultimately ensure a successful merger.
Bone morphogenetic proteins (BMPs) are biologically active proteins that are present in the human body and are regulated by different transcriptional and translational mechanisms. Bone morphogenetic proteins belong to the family of growth factors, which contribute to the processes associated with development, such as building structures and specialization tissue; in addition to the induction of the formation of bone and cartilage, these proteins also regulate cell proliferation, migration, differentiation, and apoptosis in many tissues and organs. Bone morphogenetic proteins (BMPs)have been shown to also stimulate healing of wounds and reparative processes in tissues of adult individuals. OC is morphogenetic proteins bone have been identified in humans and other animals, including BMP-2, BMP-3 (osteogenic), BMP-3b (GDF-10), BMP-4 (BMP-2b), BMP-5, BMP-6, BMP-7 (osteogenic protein-1 or OP-1), BMP-8 (OP-2), BMP-8B (OP-3), BMP-9 (GDF-2), BMP-10, BMP-11 (GDF-11, BMP-12 (GDF-7), BMP-13 (GDF-6, CDMP-2), BMP-15 (GDF-9), BMP-16, GDF-1, GDF-3, GDF-5 (CDMP-1), and GDF-8 (myostatin). Later, some of recombinant human morphogenetic proteins bone were approved by Management under the control over products and medicines of the USA for a limited clinical application. For example, INFUSE® is a commercially available product that is delivering recombinant human bone morphogenetic protein (rhBMP-2) in an absorbable collagen sponge, which can be placed in a titanium inserts for interbody fusion in the lumbar spine.
The growth factors that modulate transcription and subsequent translation morphogenetic proteins bone, strictly regulated by complex biochemical pathways. While osteogenesis can be accelerated direct application morphogenetic proteins bone, this strategy proved to be expensive and not without complications, such as erosion of the bone, inflammatory seroma, and other adverse effects.
Cation of zinc (Zn) is an important component involved in the process of bone growth. This process is at least partially mediated by zinc fingers, which are zinc-activated proteins that play is substantial role in DNA recognition as well as stimulation, regulation and expression of morphogenetic bone proteins (BMPs), and other factors that regulate bone growth, healing and bonding. Zinc fingers are some of the most common DNA-binding motifs, which contain a DNA-binding protein that resembles a finger to the base, mainly containing amino acids cysteine and histidine, which are contacted with the zinc ion. These proteins may contain more than one finger in a single chain; each structure consists of 2 antiparallel beta-folds in connection with an alpha helix. A single zinc ion is tetrahedrally coordinated conservative residues histidine and cysteine, which stabilizes the motive. Of the zinc ion plays a critical role in the stability of the protein zinc finger, because in the absence of this mineral hydrophobic core becomes too small, and biologically active domain loses its structure.
There is reliable evidence that zinc works by stimulating bone formation, which is mediated by proteins "zinc fingers", which have multiple effects in the regulation of both above and below the bone morphogenetic proteins (BMPs).
It was previously documented that the increase in the level of zinc in animal models leads to increased osteogenesis characterized by bone growth, healing, and is konstruktsii. Thus, on the basis of these results it becomes clear that it would be desirable to have an implant and a delivery system capable of regulating the optimal concentrations of zinc and other ions that are present in the environment (for example, in the bed of the spinal fusion), to stimulate osteogenesis in this particular area of interest.
The problems of the prior art are overcome with the help disclosed in the present invention various embodiments, which are devices such as medical implants, which contain a bone graft substitutes, including one or more cations, which are delivered in the local environment to stimulate osteogenesis. Private options exercise of absolute and relative concentrations of cations such as zinc, copper and/or silver, can be accurately adjusted in the desired position by changing the relative concentrations of metals in the matrix of the zeolite incorporated in the implant, or applied to the implant as well as changing the level of zeolite in the implant. This flexibility allows you to optimize the concentration of ions to deter microbial infection and formation of biofilms, which improves the regeneration of bone, and for example, promotes effective healing wounds/tissues. The zeolite in combination with the implant, t is Kim as a substitute bone graft can be used in the body of the owner, to regulate transcription and protein translation. This therapeutic strategy has a significant impact on such areas as orthopedics, spine surgery, maxillofacial surgery, cranial and neurosurgery and other applications.
In their methodological aspects of the embodiments disclosed in the present invention, relate to the stimulation of osteogenesis in need in this patient. In particular examples of implementation of the disclosed methods for modulating bone formation and mineralization comprising implanting in the body of medical implant containing a source of cations, such as ion-exchange cations. In particular examples of implementation of the medical implant is biologically active. In particular examples of the implementation of a source of cations are ion-exchange cations contained in the zeolite. In particular examples of implementation of the disclosed methods of regulating gene expression of bone morphogenetic protein (BMP) bone cells in a patient, by controlling the delivery of some cations by ion exchange through the zeolite is incorporated into the implant, such as bone substitutes entered in the patient. In accordance with private embodiments, selective gene expression of bone morphogenetic protein (BMP) may be increased (took the military expression of the gene) or lowered (inhibition or prevention of gene expression).
In particular examples of implementation implants are dental implants. A common problem with some dental implants is the lack of adhesion of the gum cells, which leads to "flooding". This causes the formation of empty pockets in the space around the implant, where bacteria breed, causing damage to the implant. Manufacturers of implants, as a rule, focus on the attachment of bone cells, but rarely on the gum cells (fibroblasts of the periodontal ligament and gingival fibroblasts). Bone morphogenetic proteins (BMPs) can lead to the proliferation of all cells at the same time, the metal cations can reduce or eliminate harmful microbes.
The embodiments disclosed in the present invention relate to the use of zeolite as a source of cations in combination with intracorporeal devices, especially medical implants, such as substitutes bone growth, for correct shipping and dispensing one or more cations, such as zinc, silver and/or copper as a tool to manage the pharmacokinetics of these cations in the local environment, to stimulate osteogenesis. The result is a unique control dosing of these cations to achieve a beneficial effect, which is often nd the need for appropriate long-released dose for many days or weeks, avoiding local cytotoxicity through a controlled release.
Biologically active protein "zinc finger" is inherently unstable, because its DNA helix depends on the Central ion zinc to ensure its stability. By infusion zinc ions locally in the area in which it is desirable formation of bone can be stabilized zinc finger, which may affect the physiological gene transcription and increased levels of bone morphogenetic proteins (BMPs) (e.g., BMP-2) and other osteogenic growth factors.
Suitable carrier materials as a source of cations include biocompatible matrix, such as demineralized bone matrix, a synthetic polymer matrix or protein matrix, such as collagen. It would be preferable to the media represented some type of bone substitutes or osteosclerosis (materials that contribute to the formation of de novo bone) agents, which would stimulate the formation of new bone through their osteoinductive and/or osteoconductive properties. Typical osteoconductive agents include matrix-based collagen, such as Healos (polymer-ceramic composite consisting of collagen fibers coated with hydroxyapatite and is indicated for spinal fusion); mA is rixy based glass; the matrices on the basis of silicate; substitutes based ceramics; substitutes-based polymer, allografts; calcium phosphates such as hydroxyapatite, tricalcium phosphate or fluorapatite; calcium sulfate; demineralized bone matrix; or any combination thereof. Typical osteoinductive agents include bone morphogenic proteins, demineralized bone matrix, various growth factors that are known to be osteoinductive (for example, transforming growth factor-beta, growth and growth differentiating factor), stem cells or stem cells with osteoblasts potential, etc. Other suitable bone graft substitutes known to experts in the art, as illustrated by the Helm and other Helm et al. "Bone Graft Substitutes for the Promotion of Spinal Arthrodesis", Neurosurg Focus 10(4) (2001), the disclosure of which is hereby incorporated by reference. In private embodiments, the bone graft configured for use in spondylosyndesis (fusion), such as stabilization of unstable spine due to structural deformation, injury, degeneration, etc. Fusion is a surgical technique in which one or more vertebrae of the spine are joined together ("fused")to reduce or eliminate relative movement between them or fix space is the result of correlation between them. Spinal splicing include posterolateral fusion, sidepassing intervertebral arthrodesis, anterior-lumbar intervertebral arthrodesis, anterior-/zadnesheynyh fusion of the thoracic spine and the interlaminar fusion. In particular examples of implementation bone grafts are inserted in the intervertebral space between adjacent vertebrae.
In particular examples of implementation, the location of the splice is placed between adjacent vertebrae, the bone graft is implanted at the specified location, and the source of metal cations present in the splicing in amounts effective to stimulate osteogenesis. In particular examples of implementation, the implant is a spinal intervertebral matrix containing cartridge containing titanium, carbon fiber, biologically compatible material, such as polyetheretherketone (PEKK), polyetherketoneketone (PEKK), or other synthetic substances. In particular examples of the implementation of the metal ions incorporated into the resin used to manufacture the implant. For example, particles of zeolite loaded with ions of zinc, silver and/or copper incorporate inside intervertebral matrix of PEEK (polyetheretherketon). In particular examples of the implementation matrix loaded osteoconductive and/or osteoinductive and agents, such as disclosed above, to stimulate splicing.
In particular examples of the implementation of intracorporeal devices include dental implants, devices (e.g., orthodontic appliances) pins, pins, caps, crowns, bridges and reinforcement of bridges, which include one or more cations, which are delivered in the local environment to stimulate osteogenesis and/or healing of the wound tissue, and/or enhancing bone regeneration; and/or inhibiting microbial infection, and/or the formation of biofilms. In particular examples of the implementation of the absolute and relative concentrations of cations such as zinc, copper and/or silver on the place in which the implant fixture, pin, pin, NIB, crown, bridge, or reinforcement of the bridge can be accurately adjusted by varying the relative concentrations of metals in the zeolite matrix, incorporated in, or applied to the implant fixture, pin, pin, handpiece, dental crown, bridge or armature bridge, as well as changing the level of zeolite in this place. The zeolite in combination with such a device can be used in the patient's body to regulate transcription and protein translation.
Such dental devices can be made from titanium or more preferably a polymer suitable for use in medicine, such as efificient (for example, PEEK (polyetheretherketon), commercially available as PEEK-OPTIMA from the company Invibio), which offers a wide combination of biocompatibility, high strength, stiffness, toughness and good aesthetics. The polymer PEEK (polyetheretherketon) shows almost the same combination of strength and bio-compatibility inherent in the metal particles, but without the negative effects. Module PEEK (polyetherketoneketone) can be attached to the bone, supporting natural fabric or natural teeth in the mouth, and thus can be used to develop metal-free dentures, which do not limit the sensation of biting or chewing. Additionally, the polymer can be easily covered and the surface is modified to accelerate bone growth and osseointegration in accordance with embodiments, disclosed in the present invention. The polymer will eliminate the electrical conductivity associated with titanium implants, and because the polymer has excellent corrosion resistance and acid resistance, it is ideal for prolonged use in a special environment of the mouth. For the preparation of zeolites used in the embodiments disclosed in the present invention can be used either natural zeolites or synthetic zeolites. "Zeolite" is an Alu is Silikat, having a three dimensional skeletal structure represented by the formula: XM2/nO·Al2O3·YSiO2·ZH2O, where M represents an ion-exchange ion, usually monovalent or divalent metal ion, n represents the atomic valence of the ion (metal), X and Y represent coefficients of metal oxide and silicon, respectively, and Z represents the number of molecules of water of crystallization. Examples of such zeolites include zeolite A-type zeolites, X-type zeolites, Y-type zeolites T-type, vysokoglinozemistyj the zeolite, sodalite, mordenite, analytic, clinoptilolite, chabazite and erionite. The zeolite can be prepared by replacing some or all of the ions in the ion-exchange zeolite (for example, sodium ions, calcium ions, potassium ions, iron ions) to ammonium ions and zinc ions of silver and/or copper, as disclosed in U.S. patent No. 4939958 and 4911898, the full disclosure of which is incorporated into this description by reference. The number of ions of zinc, silver and/or copper in the zeolite should be sufficient to ensure that they were present in amounts effective to stimulate osteogenesis in the period of time required for bone substitution in combination with one or more osteoarthrosis agents and implanting in the body. The typical amount includes from about 50 ppb to approximately 1000 ppb zinc ions and/or from approximately 20 ppb to 200 ppb of copper ions and/or silver. Preferably, the zinc was largely represented than copper, usually about four times the concentration of copper. In specific embodiments, the metal cation is present at a level lower ion exchange capacity of at least part of the zeolite particles.
To form the zeolite with the appropriate number of ions in specific embodiments, ions are incorporated into the solution by the suspension, for example, 50 wt.% the zeolite powder of type a in the water. Silver nitrate, copper nitrate and zinc nitrate with nitric acid added to the water. Typical concentrations of metal salts are in the range between 1 and 10%.
Solutions of metal ions is poured into a vessel for mixing and suspension of zeolite quickly added to the vessel with vigorous stirring and at a temperature of approximately 75°C.
The suspension is subjected to ion exchange within 1 to 24 hours. It is filtered and washed with distilled water. The suspension is dried at a suitable temperature to 200°C. After drying the suspension is ground to particles of the appropriate size.
The relative concentration of metals in solution will be to determine their value at boot time. Concentration, temperature and time of the exchange will determine the total load of metals. The methods disclosed in U.S. patent No. 5256390, RAS is the freight which, in the present description are incorporated by reference, also are appropriate.
Zeolites can be obtained in masterbatches pellets of low density polyethylene, polypropylene, ultrahigh-molecular weight polyethylene or polystyrene, containing a suitable amount of particles of zeolite, usually 20 wt.% particles of the zeolite. Under the condition of existence in this form, the resin beads containing particles of zeolite, can be easily blended with the resin used for the production of implants, or used for the production of coatings that will be applied to the implant, as described in U.S. patent No. 6582715, the disclosure of which is incorporated into this description by reference. The typical number of particles of the zeolite is incorporated in the resin for implantation is in the range from 0.01 to 10 wt.%, more preferably from 0.01 to 8.0 wt.%, most preferably from 0.1 to 5.0 wt.%. The method used to cover the implant, nothing special is not limited and may include spraying, painting or dipping. When compounding in PEEK (polyetheretherketon), for example, PEEK (polyetheretherketon) must be protected from moisture and contamination. Compounding can be carried out by stirring.
1. Substitute bone graft containing osteogenic agent and zeolite containing particles containing ion exchange metal cations present the number effective for stimulation of osteogenesis in need in this patient, which of the above cations of metals selected from the group consisting of zinc ions, silver ions, copper ions, and combinations thereof.
2. The bone graft substitute of claim 1, wherein the above metal cation is zinc.
3. Substitute bone graft according to claim 1, in which the above osteogenic agent selected from the group consisting of osteoinductive agents, osteoconductive agents, and combinations thereof.
4. Substitute bone graft according to claim 3, in which the above osteoinductive agent selected from the group consisting of bone morphogenetic protein, demineralized bone matrix, osteoinductive growth factor, osteoblast and stem cells.
5. Substitute bone graft according to claim 3, in which the above osteoconductive agent selected from the group consisting of matrix-based collagen, matrix-based glass matrix based on silicate, substitute based ceramics, substitute-based polymer, allografts, calcium phosphates, tricalcium phosphate, fluorapatite, calcium sulfate, demineralized bone matrix, and combinations thereof.
6. The implant containing osteoplastic agent and zeolite containing particles containing ion-exchange cations of the metals present in the amount effective to stimulate osteogenesis in need in this patient, which of the above cations selected from the group consisting of zinc ions, silver ions, copper ions, and combinations thereof.
7. The implant according to claim 6, in which the above metal cation is zinc.
8. The implant according to claim 6, in which the above osteogenic agent selected from the group consisting of osteoinductive agents, osteoconductive agents, and combinations thereof.
9. The implant according to claim 6, in which the above implant contains synthetic bone.
10. The implant according to claim 6, where the above implant is an interbody spinal tank.
11. Method for modulating bone formation and mineralization, including the implantation of the subject of the bioactive implant containing an effective amount of an agent that modulates bone morphogenetic proteins, and ion-exchange cations of metals present in amounts effective to stimulate osteogenesis in the above subject, in which the above metal cations selected from the group consisting of zinc ions, silver ions, copper ions, and combinations thereof.
12. The method according to claim 11, in which the above metal cation is zinc.
13. The method according to claim 11, in which the above osteogenic agent selected from the group consisting of OST is inducting agents, osteoconductive agents, and combinations thereof.
14. Intracorporeal device containing osteoarthrosis agent and zeolite containing particles containing ion-exchange cations of metals present in amounts effective to stimulate osteogenesis in need in this patient, which of the above cations of metals selected from the group consisting of zinc ions, silver ions, copper ions, and combinations thereof.
15. Intracorporeal device 14, in which the above-mentioned cation is zinc.
16. Intracorporeal device 14, in which the above osteogenic agent selected from the group consisting of osteoinductive agents, osteoconductive agents, and combinations thereof.
17. Intracorporeal device 14, in which the above device is a device selected from the group consisting of a dental implant fixture, pin, pin, tip, crowns, bridge and valve bridge.
SUBSTANCE: group of inventions refers to medicine, namely to gynaecology, and can be used in treating such diseases as dysfunctional uterine bleeding, menorrhagia, dysmenorrhoea, endometriosis, uterine fibroid, menopausal disorders, osteoporosis and urogenital atrophy. That is ensured by presenting an urogenital system comprising a frame forming an internal cavity enclosing an insert with a therapeutically effective dose of a biologically active compound. The insert is form-stable and damage-resistant when in use. The frame has an open structure providing access to a main portion of an external portion of the insert. The frame comprises one or more retaining element for frame holding in the uterine. What is also presented is a method for making the above intrauterine system.
EFFECT: group of inventions provides an effective controlled release drug delivery for a long period of time, as well as easy and safe administration and proper removal of the preparation.
14 cl, 9 dwg
SUBSTANCE: composition contains ceftazidime, eucalyptus oil, dexamethasone, lidocaine hydrochloride and mixture of talcum powder with Vaseline and glycerol in certain relations. A base of the composition in the form of a suppository is mixture of Vaseline and glycerol with talcum powder.
EFFECT: composition is effective for treating bacterial external otitis ensured by its dosage form and the integrated effect of therapeutic ingredients.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics, namely to a formulation for oral transmucosal administration which contains a lipid-lowering active substance specified in statins, fibrates or ezetimibe; an aqueous-alcohol solution consisting of water and 30° to 70° ethanol, wherein the above active substance is found in a stable and completely dissolved state with the pH value of the formulation falling within the range of 5.0 to 8.0. The invention also refers to a method for preparing the above formulation and using it for treating hyperlipidemia.
EFFECT: invention provides better efficacy for lower doses of the active substances (statins, fibrates and ezetimibe); their immediate bioavailability for hepatocytes and considerably reduced production of harmful metabolites that stands for eliminating the main side effects of these agents.
11 cl, 6 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to the pharmaceutical industry and represents a liquid pharmaceutical composition for improving at least one medical condition requiring administration of an adrenergic compound into an individual; the pharmaceutical composition contains the adrenergic compound, wherein the adrenergic compound is epinephrine or its physiologically acceptable salt, and at least one antioxidant specified in a group consisting of bisulphite, metabisulphite and sulphite compounds, wherein a molar ratio of the adrenergic compound to at least one antioxidant measured as a sulphite equivalent falls within the range of 0.70-1.30 and wherein the pH value of the above liquid composition falls within the range of 2.0-5.0.
EFFECT: invention provides higher storage stability with substantially reduced sensitivity to induced light, thermal and oxidative degradation.
17 cl, 9 dwg, 3 ex
SUBSTANCE: invention relates to a stable liquid pharmaceutical composition, which includes 3-(2,2,2-trimethylhydrazinium)propionate-2-ethyl-6-methyl-3-hydroxypyridine disuccinate in amount of 0.1-50 wt %, auxiliary substances in amount of 0.01-50 wt % and water.
EFFECT: invention enables to obtain stable pharmaceutical compositions for injection, peroral and local application, having marked antihypoxic, antioxidant and adaptogenic action.
32 cl, 1 dwg, 14 tbl, 60 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry and represents a liquid pharmaceutical composition for relieving at least one symptom of a disease which requires an adrenergic compound representing adrenalin or its physiologically acceptable salt, and at least one antioxidant specified in a group consisting of bisulphite, metabisulphite and a sulphite compound; a molar ratio of the adrenergic compound and at least one antioxidant specified as sulphite ion equivalents is within the range of 1.31-2.20, while pH of the above liquid composition is found within the range of 2.0-5.0.
EFFECT: invention provides higher storage stability with substantially reduced sensitivity to induced light, thermal and oxidative degradation.
16 cl, 3 ex, 9 dwg
SUBSTANCE: group of inventions relates to medicine, namely to cosmetology, and can be used for treatment of skin aging. For this purpose, used is a medication, which contains a basic fibroblast growth factor (bFGF) as a single active ingredient, which is introduced intracutaneously or subcutaneously into the place of a scar or into the surrounding region, for instance, a keloid, a hypertrophic scar and a scar contracture; in addition, the medication is also intended for treatment of one or more types of skin aging, selected from the following list: skin wrinkles, sagging skin, rough skin, skin thinning and reduction of skin resilience and elasticity because of rupture of dermal tissues or reduction of functions of fibroblast cells, with skin aging being photoaging, and a value of a dose of the basic fibroblast growth factor (bFGF) constituting from 0.1 mcg to 1 mg per 1 cm2 of skin, which represents the treatment target.
EFFECT: inventions ensure significant reduction of wrinkles, improvement of the skin structure, as well as due to an increase of its turgor and an increase of the volume of the subcutaneous adipose cellular tissue.
6 cl, 4 ex, 10 dwg
FIELD: food industry.
SUBSTANCE: invention relates to anti-reflux food. One proposes application of a thickener for production of a nutritional composition for prevention of gastroesophageal reflux and/or for prevention and/or treatment of gastrointestinal reflux disease. The said nutritional composition includes whey protein and/or casein, a thickener, chosen from the group consisting of locust bean gum, tara gum, tragacanth gum, guar gum and fenugreek gum, and a fermented milk product. The total quantity of whey protein and/or casein accounts for less than 15 wt % of the total weight of the composition in terms of dry substances. The composition contains less than 1.6 g of protein per 100 ml of the liquid product. The fermented milk product quantity accounts for 5 - 70 wt % of the total weight of the product in terms of dry substances.
EFFECT: invention allows to reduce the thickener quantity in the product for children at an early age with preservation of anti-reflux properties as well as manufacture thicker product.
23 cl, 4 tbl, 7 ex
SUBSTANCE: what is described is a biodegradable haemostatic therapeutic agent for control of bleeding, which provides co-immobilising ε-aminocapronic acid 50 mg, lysozyme 5 mg in distilled water 6.5 l for 3 hours at room temperature for dialdehyde cellulose 1 g at a degree of oxidation 12%. The material is pressed out and dried to residual moisture no more than 10% in the air in darkness. After having dried, the material is milled in a fine mill to particles having a size of 20 to 50 mcm. A rate of control of bleeding is 102 seconds. A time of total resorption is 10 days.
EFFECT: agent provides a high degree of hydrolytic destruction and a good haemostatic activity.
4 cl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to pharmacy and medicine, and concerns a composition, a method and a kit which enable a controlled release of octreotide, e.g. octreotide acetate in an individual. The composition contains a preparation containing octreotide basically enclosed in a hydrophilic polymer specified in polyurethane polymers and methacrylate polymers; it is effective for providing octreotide release at a rate of 30 mcg to 800 mcg a day for six months in vivo, wherein the hydrophilic polymer, but not the preparation, additionally contains a releasing substance with molecular weight of at least approximately 1,000 Dalton, wherein the preparation contains octreotide 40 to 120 mg, and the releasing substance is specified in a group consisting of Brij 35 (polyoxyethylene lauryl ester), polyoxyethylene(20)sorbitan trioleate, Tween 20, Tween 80, vitamin E TPGS and mixtures of any of the two or more.The method for reducing GH levels or IGF-1 levels and/or treating an octreotide-sensitive disease involving a subcutaneous implantation of at least one dry implanted device comprising the declared preparation. The kit comprising the declared composition for octreotide controlled release.
EFFECT: group of inventions provides a therapeutically effective amount of octreotide for a long period of time with treating hormonal conditions.
25 cl, 11 ex, 7 tbl, 21 dwg
SUBSTANCE: experimental wound is cleaned daily, first with normal saline (NaCl), and then coated with modified montmorillonite clay containing 0.1 to 4.35 wt % of silver. The preparation is introduced into the wound in an amount of 0.1 g per a wound of 1.5 cm in diameter.
EFFECT: higher rate of septic wound healing.
3 tbl, 3 dwg
SUBSTANCE: invention relates to compositions and polymeric materials for biomedical use, comprising silver nanoparticles (0.0005-0.02 wt %) stabilised by amphiphilic copolymers of maleic acid (0.0008-0.05 wt %), low molecular weight organic amines (0.0002-0.04 wt %) and water. In addition, the said composition may additionally comprise the polymeric structure-forming agent.
EFFECT: introduction to the composition of the polymer structure-forming agent enables to obtain the macroporous structured hydrogel materials having prolonged bactericidal and antifungal action.
3 cl, 2 tbl, 9 ex
SUBSTANCE: inorganic clay, represented by sodium-calcium, and/or calcium and/or ferrous forms of montmorillonite, is modified with a water solution of silver nitrate with a concentration 0.16-9.9 wt % in a weight ratio clay:water solution of silver nitrate 1:5. Modification is carried out with mixing from 3 to 7 hours at a temperature in the interval from 10°C to the temperature of boiling. The obtained material is washed with distilled water to pH ≈6-5, until excess of silver nitrate is removed, stood at room temperature and decanted. The material is dried at a temperature of 20-160°C.
EFFECT: obtaining an efficient antibacterial material for traditional and veterinary medicine.
2 tbl, 5 ex
SUBSTANCE: in a complex preparation containing a carrier representing an enterosorbent; the enterosorbent is modified by immobilising high-disperse silver - nanosilver in a concentration of 0.01 - 1.0 wt % on its surface. The enterosorbent represents activated carbon, kaolin, bentonit, or enterodesum, or monocrystalline cellulose. A modifying silver-containing solution - a nanosilver source - is silver clusters in an aqueous solution.
EFFECT: higher specific antimicrobial activity.
2 cl, 3 tbl, 2 ex
SUBSTANCE: composition contains the bactericidal substance Poviargol in the amount of 2.1-7.0 wt % and zosterin in the amount of 1.1-7.0 wt %.
EFFECT: synergetic action of the ingredients of the composition and promotion of the anti-inflammatory, radio protective, reparative action.
SUBSTANCE: invention relates to medicine and specifically to trauma surgery and orthopaedics, and can be sued for surgical treatment of ununited fractures and false joints of cylindrical bones when there is a shortage of soft tissue. The method involves, 5-6 days before an operation, performing needle biopsy of bone and soft tissue fragments from the damage centre of the cylindrical bone and determining presence and nature of obligate intracellular viral infection (OIVI). Super-selective angiographic analysis of the microvascular channel to the capillary link is also performed. Valtrex is administered to the patient 2-4 days before the operation in a dose of 500 mg twice a day. Further, the method involves performing osteosynthesis or re-osteosynthesis with resection of the ends of bone fragments, opening marrowy canals, bone stimulation and batting the space of the bone defect with a gel-like nanostructured composite implant. In the presence of OIVI, resection of bone fragments is carried out in a larger volume until the onset of "pinpoint bleeding", i.e. to areas with satisfactory intrabone blood supply. The composite implant contains thrombocyte-rich autoplasma, mixed in ratio of 1:(1-2) with granules of a complex alloplastic preparation (CAP) based on hydroxyapatite which contains 50-60 wt % collagen. The composite implant also contains either 0.08-2.8 wt % colloidal solution of nanoparticles of zero-valent silver metal Ag0, or gold Au0, or copper Cu0, or palladium Pd0, or platinum Pt0, or 5-12 wt % nanoparticles of said metals in dry form. The nanoparticles have size of 2-40 nm. A colloidal solution of said nanoparticles or colloidal nanoparticles of said metals in dry form is added to the CAP granules. Further, the prepared granules of the gel-like complex alloplastic preparation are laid in a selected ratio on the layer of thrombocyte-rich autoplasma, without mixing, for subsequent transfer into the bone defect space. In case of performing resection of bone fragments in a larger volume until the onset of "pinpoint bleeding", corticotomy is further performed on the cylindrical bone being operated on, with subsequent distraction of the bone regenerate using any existing method. Further, the bone fragments are repositioned, followed by metallo-osteosynthesis. Before wound suturing, the surface of the area with shortage of soft tissue in the projection of the ununited fracture and false joints is covered by a semi-permeable flexible plate made of the complex alloplastic preparation based on hydroxyapatite, which contains 50-60 wt % collagen. The plate has thickness of 0.25-1.2 mm. The surface area of the plate is 10-20% greater than the area with shortage of soft tissue in the corresponding projection. The part of the erythrocyte mass remaining from preparing the thrombocyte-rich autoplasma and the plasma are returned into the bloodstream of the patient by intravenously using a drip during the surgical procedure or in the early post-operation period. After the operation, valtrex is administered to the patient in a dose of 500 gm once a day for two weeks and then in a dose of 500 mg every other day for two weeks.
EFFECT: method provides reliable prevention of OIVI at a damage centre, normalisation of local microcirculation of blood, avoiding ischemic processes, and compensation for the shortening of the length of the limb of the patient being operated on while preventing weakening of the process of reparative osteogenesis and allergic reactions of the body.
6 cl, 4 ex
SUBSTANCE: invention represents a pharmaceutical composition for treating local manifestations of herpes simplex infections and for preventing influenza and acute respiratory viral infections, containing green tea extract and epigallocatechin-3-gallate (EGCG) 70-90 wt %, colloidal silver and a gel-forming base with the ingredients of the composition taken in certain ratio, wt %.
EFFECT: high clinical effectiveness.
6 cl, 8 ex, 5 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed is application of preparation DAM+™ for injection treatment of gastroesophageal reflux (gastroesophageal reflux disease).
EFFECT: described is recovery of locking function of gastroesophageal junction with absence of migration, which contributes to extension of arsenal of medications used for treatment of the disease.
5 dwg, 1 tbl
SUBSTANCE: invention refers to using ultradisperse silver-containing systems as anti-inflammatory, anti-exudative and wound-healing agents. The ultradisperse silver-containing systems represent zero-valent silver metal nanocomposites at particle size 10-25 nm stabilised with arabinogalactine and its sulphated derivative. The invention also refers to an agent for wound and burn healing having anti-inflammatory, anti-exudative, wound-healing and antimicrobial activity, comprising said silver nanocomposites as a pharmacologically active substance and additionally containing carbomer, triethanolamine, glycerol or 1,2-propylene glycol and water. The agent is presented in the form of topical hydrophilic gel. The invention also refers to using the above agent for wound and burn healing in an individual in need thereof.
EFFECT: declared invention provides creating the hydrophilic gels of silver nanocomposites that are applicable for wound and burn healing.
3 cl, 8 dwg, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to a topical preparation for contaminated wound healing. The above preparation contains lidocaine hydrochloride 0.1-0.2%, thrombolysin 30-36%, metronidazole 0.25-0.5%, clindamycin 0.3-0.45%, rifampicine 0.45-0.6%, olive oil 10%, sea buckthorn oil 1.5-2.0%, starch 5.1% and silver water.
EFFECT: invention promotes reducing contaminated wound complications, provides the advance of antibacterial active substances through intertissue spaces to the deep tissues with faster pathogenic flora inhibition in a wide range.
2 cl, 2 ex
SUBSTANCE: endodontic treatment stage involving retrieval and dilation of a root canal is performed. Gluftored liquid is introduced into the root canal of the tooth. A fibre cable is placed above a tooth canal orifice, and the liquid is reflected by means of a laser light for 30-60 seconds. The root canal is dried with a paper point. Pre-shaken Gluftored suspension is introduced into the root canal. The fibre cable is placed above the tooth canal orifice, and the suspension is reflected by means of the laser light for 30-60 seconds. The root canal is dried and filled.
EFFECT: method provides higher clinical effectiveness in the patients with dental pulp and periodontal diseases by activating the course of chemical reactions in mineralising liquid and suspension, crystal obturation of dentine tubes and closing a microbial invasion propagation path into the periodont to be protected against toxins and tissue disintegration products, forming a single mineral complex of the liquid, suspension and dentine of the root canal of the tooth, photobiostimulation of periodontal microcirculation by means of low intensity laser light energy, the presence of copper ions provides the permanent bactericidal effect.
10 dwg, 1 ex